Linked Life Data

8288597

Source:http://linkedlifedata.com/resource/pubmed/id/8288597

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-2-22
pubmed:abstractText
The enhancer of the rat ornithine transcarbamylase gene is located 11 kilobases upstream from the transcription start site and has been shown to be hepatoma cell-specific. Using transgenic mice, we showed that this enhancer is capable of activating transcription in a liver-specific manner, inverting the tissue specificity of the homologous promoter that is by itself more active in the small intestine than in the liver. Transient transfection analysis with cultured hepatoma cells indicated that the enhancer activity resides in the approximately 110-base pair region containing four protein-binding sites, two for hepatocyte nuclear factor-4 (HNF-4) and two for CCAAT/enhancer binding protein (C/EBP), both of which are liver-selective transcription factors. Concatemerization of a region containing one HNF-4 and one C/EBP site led to reconstitution of the hepatoma cell-specific enhancer, and intactness of these two sites was strictly required for the enhancer activity. Furthermore, cotransfection experiments showed that both HNF-4 and C/EBP beta are necessary, and neither alone sufficient, for activation of the reconstituted enhancer in nonhepatic cells. Requirement of combinatorial operation of at least two liver-enriched transcription factors for transcriptional activation successfully explains why these liver-selective but not strictly liver-specific factors can confer more restricted liver specificity on transcription of their target genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1323-31
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8288597-Animals, pubmed-meshheading:8288597-Base Sequence, pubmed-meshheading:8288597-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, pubmed-meshheading:8288597-Binding Sites, pubmed-meshheading:8288597-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:8288597-CHO Cells, pubmed-meshheading:8288597-Cricetinae, pubmed-meshheading:8288597-DNA Primers, pubmed-meshheading:8288597-DNA-Binding Proteins, pubmed-meshheading:8288597-Enhancer Elements, Genetic, pubmed-meshheading:8288597-Female, pubmed-meshheading:8288597-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8288597-Hepatocyte Nuclear Factor 4, pubmed-meshheading:8288597-Liver, pubmed-meshheading:8288597-Male, pubmed-meshheading:8288597-Mice, pubmed-meshheading:8288597-Mice, Transgenic, pubmed-meshheading:8288597-Molecular Sequence Data, pubmed-meshheading:8288597-Nuclear Proteins, pubmed-meshheading:8288597-Ornithine Carbamoyltransferase, pubmed-meshheading:8288597-Phosphoproteins, pubmed-meshheading:8288597-Promoter Regions, Genetic, pubmed-meshheading:8288597-Sequence Deletion, pubmed-meshheading:8288597-Structure-Activity Relationship, pubmed-meshheading:8288597-Tissue Distribution, pubmed-meshheading:8288597-Transcription, Genetic, pubmed-meshheading:8288597-Transcription Factors, pubmed-meshheading:8288597-Transfection
pubmed:year
1994
pubmed:articleTitle
Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors. Both HNF-4 and C/EBP beta are required for liver-specific activity of the ornithine transcarbamylase enhancer.
pubmed:affiliation
Department of Molecular Genetics, Kumamoto University School of Medicine, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't